AIM： To investigate the anti-（lymph）angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty（PK） model. METHODS： Graft survival, corneal neovascularizatio...AIM： To investigate the anti-（lymph）angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty（PK） model. METHODS： Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline（PBS） and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction（RT-PCR） was performed to quantify the expression of inflammatory cytokines（TNF-alpha, IL-6） and vascular endothelial growth factor（VEGF）-A, VEGF-C, VEGFR-2, and VEGFR-3.RESULTS： In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group（all P〈0.05）. The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group（all P〈0.05）. In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group（P=0.057, 0.096, 0.012, respectively）. The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group（all P〈0.05）.CONCLUSION： Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-（lymph）-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.展开更多
文摘AIM： To investigate the anti-（lymph）angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty（PK） model. METHODS： Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline（PBS） and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction（RT-PCR） was performed to quantify the expression of inflammatory cytokines（TNF-alpha, IL-6） and vascular endothelial growth factor（VEGF）-A, VEGF-C, VEGFR-2, and VEGFR-3.RESULTS： In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group（all P〈0.05）. The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group（all P〈0.05）. In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group（P=0.057, 0.096, 0.012, respectively）. The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group（all P〈0.05）.CONCLUSION： Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-（lymph）-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.
